The long term goal for the proposed research is to develop a gene therapy approach directed to pluripotent hematopoietic stem cells (HSC) to reduce AIDS using the SIV-rhesus macaque model. HSC are attractive targets for gene therapy because transduced HSC have the capacity to permanently reconstitute the hematopoietic and immune systems. Preliminary research in our laboratory demonstrates that we can transduce rhesus macaque bone marrow in vivo retroviral vectors. We have observed marked lymphoid cells, in particular CD4+ T-cells, in the peripheral circulation for up to six months post-transplantation. We hypothesize that in vivo transduction of rhesus macaque HSC with anti-SIV-1 genes will lead to the permanent reconstitution of the immune system with CD4+ lymphocytes that will inhibit SIV replication and aid in the reconstitution of a functional immune system. The research objectives of phase 1 will investigate methods to improve levels and expression of genes transferred in vivo into rhesus macaque HSC and ultimately CD4+ T-cells. Research objectives of phase 2 are to design and construct specific anti-SIV gene cassettes for their abilities to reduce viral loads and AIDS in vivo. Dr. Newbound is an outstanding SERCA candidate with exceptional academic ability (DVM, MSc, PhD. Dipl. ACVM). He has worked with animal models of retroviral diseases prior to, and during his two graduate programs. Dr. Newbound has expertise in both immunology and virology as evidenced by his certification by the American College of Veterinary Microbiologists. Dr. Newbound has demonstrated a strong commitment to becoming an independent academic investigator. The sponsors and sponsor provide an outstanding environment for developing the technical skills necessary complete this work in a highly productive research- oriented academic atmosphere. Additionally, the candidate will work extensively with the co-sponsor, a board-certified laboratory animal veterinarian, to learn primate laboratory animal medicine that will enable him to use these models throughout his career.